Aging Macaca nigra develop impaired glucose tolerance (IGT) as a result of a lesion in the islets of Langerhans. The syndrome is similar to that likely present in millions of older Americans. The islet lesion, characterized by the appearance of a specific form of amyloid, occurs concurrent with alterations in secretory cell structure and function, increased glucagon, impaired insulin response, and precedes IGT after sexual maturity. Isolation and characterization of human and monkey islet amyloid protein will allow understanding of amyloid origin, whether from secretory cell hormonal polypeptides or from external sources such as immunoglobulins. Knowledge of its origin would direct attempts at understanding causes and at prevention. Antibodies generated against purified amyloid will be used to search for blood markers indicative of the lesion in monkeys and in human beings. Rhesus monkey lymphocyte antigens (RhL-A) and protein polymorphisms will be used for phenotypic and genotypic characterization of Macaca nigra. Correlations will be sought between the lesion with its resultant IGT, and specific genetic markers (analogous to HLA linkages with human juvenile diabetes); establishment of IGT patterns in familial interrelationships make directed breeding possible. Islet cell antibodies (ICA) may arise in response to islet cell deterioration or may even contribute to development of the lesion. Longitudinal monitoring for ICA in blood of juvenile monkeys as they mature will allow exact correlations between the earliest stages of the islet lesion and the hormonal changes that occur before clinical detection of IGT. Relatively mild glucose intolerance of long duration in older human beings is associated with development of pathologic changes. Understanding this syndrome in Macaca nigra provides direction for the assessment, prevention, and amelioration of a similar condition in aging human beings.